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Tumor cell-matrix interaction: pericellular matrix degradation and metastasis
1Department of Pathology, School of Medicine, Keio University, Tokyo, Japan.
Verhandlungen Der Deutschen Gesellschaft Fur Pathologie
|February 24, 2001
Summary
Matrix metalloproteinases (MMPs) are crucial for cancer invasion and metastasis. This study identifies specific MMPs, like MMP-2 and MT1-MMP, involved in various human cancers, highlighting their role in extracellular matrix degradation.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are implicated in cancer progression.
- Specific MMPs and their activation mechanisms vary across different cancer types.
Purpose of the Study:
- To identify key MMPs involved in invasion and metastasis across diverse human cancers.
- To elucidate the roles of specific MMPs, including membrane-type MMPs (MT-MMPs), in cancer cell invasion.
Main Methods:
- Expression analysis of ten MMPs and two TIMPs in multiple human cancer types.
- In situ zymography to assess gelatinolytic activity within carcinoma cell nests.
- Investigation of brevican degradation by MMPs and ADAMTS4 in gliomas.
Main Results:
- ProMMP-2 activation by MT1-MMP is critical for invasion in most cancers studied, except endometrial carcinoma.
- ProMMP-7 activation drives lymph node metastasis in endometrial carcinomas.
- MT1-MMP and MT2-MMP contribute to proMMP-2 activation in gliomas, with decreased TIMP-2 and increased MT1-MMP facilitating glioblastoma cell spread.
- Glioma invasion may involve brevican degradation by activated MMP-2 and ADAMTS4.
Conclusions:
- Extracellular matrix-degrading MMPs, particularly those on cancer cell membranes, are essential for human cancer invasion and metastasis.
- Targeting specific MMPs like MMP-2 and MT1-MMP presents potential therapeutic strategies for various cancers.